rs2302387

Positions:

chr7-87462869-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000443.4(ABCB4):c.175C>T(p.Leu59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,612,594 control chromosomes in the GnomAD database, including 24,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5350 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18873 hom. )

Consequence

ABCB4
NM_000443.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.790

Variant links:

Genes affected

ABCB4 (HGNC:45): (ATP binding cassette subfamily B member 4) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function. [provided by RefSeq, Jul 2008]

ABCB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 7-87462869-G-A is Benign according to our data. Variant chr7-87462869-G-A is described in ClinVar as [Benign]. Clinvar id is 256158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87462869-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB4	NM_000443.4 linkuse as main transcript	c.175C>T	p.Leu59=	synonymous_variant	4/28	ENST00000649586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB4	ENST00000649586.2 linkuse as main transcript	c.175C>T	p.Leu59=	synonymous_variant	4/28		NM_000443.4	P1	P21439-2

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34844

AN:

151828

Hom.:

5330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.170

AC:

42718

AN:

251194

Hom.:

4392

AF XY:

0.164

AC XY:

22247

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.194

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.152

AC:

222260

AN:

1460648

Hom.:

18873

Cov.:

AF XY:

0.151

AC XY:

109789

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.230

AC:

34914

AN:

151946

Hom.:

5350

Cov.:

AF XY:

0.226

AC XY:

16814

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.160

Hom.:

4779

Bravo

AF:

0.241

Asia WGS

AF:

0.188

AC:

655

AN:

3478

EpiCase

AF:

0.144

EpiControl

AF:

0.144

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Cholestasis, intrahepatic, of pregnancy, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Progressive familial intrahepatic cholestasis type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.2

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over